926 resultados para type III secretion
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The importance of partial redistribution (PRD) in the modelling of the Lyman a and Lyman ß emission lines of hydrogen in stellar atmospheres is examined using simple atmospheric models of a range of late-type stars. These models represent the subgiant Procyon (F5 IV-V), and the two giants ß Gem (K0 III) and a Tau (K5 III). These stars are selected to span a wide range of surface gravities: 1.25 <log g <4.00. The calculations are performed using the computer code MULTI with the modifications made by Hubeny & Lites. It is found that PRD effects are highly significant, both in the direct prediction of the Lyman line profiles and in the application of hydrostatic equilibrium to calculate the atmospheric electron density in static atmospheric models.
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Gelsolin is a cytoskeletal protein which participates in actin filament dynamics and promotes cell motility and plasticity. Although initially regarded as a tumor suppressor, gelsolin expression in certain tumors correlates with poor prognosis and therapy-resistance. In vitro, gelsolin has anti-apoptotic and pro-migratory functions and is critical for invasion of some types of tumor cells. We found that gelsolin was highly expressed at tumor borders infiltrating into adjacent liver tissues, as examined by immunohistochemistry. Although gelsolin contributes to lamellipodia formation in migrating cells, the mechanisms by which it induces tumor invasion are unclear. Gelsolin's influence on the invasive activity of colorectal cancer cells was investigated using overexpression and small interfering RNA knockdown. We show that gelsolin is required for invasion of colorectal cancer cells through matrigel. Microarray analysis and quantitative PCR indicate that gelsolin overexpression induces the upregulation of invasion-promoting genes in colorectal cancer cells, including the matrix-degrading urokinase-type plasminogen activator (uPA). Conversely, gelsolin knockdown reduces uPA levels, as well as uPA secretion. The enhanced invasiveness of gelsolin-overexpressing cells was attenuated by treatment with function-blocking antibodies to either uPA or its receptor uPAR, indicating that uPA/uPAR activity is crucial for gelsolin-dependent invasion. In summary, our data reveals novel functions of gelsolin in colorectal tumor cell invasion through its modulation of the uPA/uPAR cascade, with potentially important roles in colorectal tumor dissemination to metastatic sites.
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Diabetes may induce both quantitative and qualitative changes in lipoproteins, especially low-density lipoprotein (LDL). Effects of LDL glycation on endothelial cell secretion of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) have not been fully elucidated. Human aortic endothelial cell (HAEC) tPA and PAI-1 production were determined after incubation with LDL (50 to 500 microg/mL protein, 24 h) from three sources: (1) nondiabetic LDL (N-LDL) modified in vitro to form six preparations: native, nonmodified (N); glycated (G); minimally oxidized (MO); minimally oxidized and glycated (MOG); heavily oxidized (HO); and heavily oxidized and glycated (HOG); (2) in vivo glycated and relatively nonglycated LDL subfractions from type 1 diabetic patients; (3) LDL from type 1 diabetic patients and matched controls, which was subfractionated using density gradient ultracentrifugation. In experiments using LDL modified in vitro, the rate of tPA release by HAECs incubated with N-LDL (83 +/- 4 ng/mg cell protein/24 h) did not differ significantly from those incubated with G-LDL (73 +/- 7), MO-LDL (74 +/- 13), or MOG-LDL (66 +/- 15) and was not influenced by LDL concentration. The rate of PAI-1 release was similar in HAECs incubated with N-LDL (5.7 +/- 0.6 mug/mg cell protein/24 h), G-LDL (5.7 +/- 0.7), MO-LDL (5.5 +/- 0.8), or MOG-LDL (5.7 +/- 0.9) and was not influenced by LDL concentration. In contrast, tPA release was significantly decreased in cells incubated with LDL (10 microg/mL) modified extensively by oxidation, and averaged 45.2 +/- 5.0 and 43.7 +/- 9.9 ng/mg/24 h for HO-LDL and HOG-LDL, respectively, and was further decreased with increasing concentrations of the heavily oxidized LDL preparations. PAI-1 release was not significantly decreased relative to N-LDL in cells incubated with low concentrations (5 to 50 microg/mL) of HO-LDL and HOG-LDL, but was decreased to 3.2 +/- 0.5 and 3.1 +/- 0.7 microg/mg/24 h for HO-LDL and HOG-LDL at 200 microg/mL, respectively. Results using in vivo glycated versus nonglycated LDL showed that tPA and PAI-1 release did not differ between subfractions. Release of tPA averaged 5.11 +/- 0.6 and 5.12 +/- 0.7 ng/mg/24 h, whereas release of PAI-1 averaged 666 +/- 27 ng/mg/24 h and 705 +/- 30 ng/mg/24 h for nonglycated and glycated LDL subfractions, respectively. Using LDL of different density subclasses, tPA and PAI-1 release in response to LDL from diabetic patients compared with control subjects did not differ when HAECs were incubated with LDLs of increasing density isolated from each subject pair. We conclude that oxidation of LDL, but not glycation, may contribute to the altered fibrinolysis observed in diabetes.
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The very low- and low-density lipoprotein fractions were isolated from 16 normolipidaemic Type 2 (non-insulin-dependent) diabetic patients in good to fair glycaemic control and from corresponding age-, sex-, and race-matched, non-diabetic control subjects. Rates of cholesteryl ester synthesis averaged 268 +/- 31 vs 289 +/- 40 pmol 14C-cholesteryl oleate.mg cell protein-1.20 h-1 for very low- and 506 +/- 34 vs 556 +/- 51 pmol 14C-cholesteryl oleate.mg cell protein-1.20 h-1 for low-density lipoproteins isolated from the Type 2 diabetic patients and control subjects, respectively, when they were incubated with human macrophages. A group of approximately one-third of the patients was selected for separate analyses because very low-density lipoproteins isolated from these patients did stimulate more cholesteryl ester synthesis when incubated with macrophages. There were no significant differences in the lipid composition of the lipoproteins isolated from the three groups of subjects. The relative proportion of apoprotein C to apoprotein E was significantly decreased (p less than 0.002) in the very low-density lipoproteins from diabetic patients and was further decreased in samples from these selected diabetic patients. The apoprotein C-I content of very low-density lipoproteins isolated from diabetic patients was increased compared to control subjects and was further increased in samples from the selected diabetic patients (p less than 0.02). There were no significant differences in the proportions of apoproteins C-III-0, C-III-1, or C-III-2 among the three groups. These studies suggest that in normolipidaemic Type 2 diabetic patients, the apoprotein composition of VLDL is abnormal and this may alter VLDL macrophage interactions and thus contribute to the increased prevalence of atherosclerosis in diabetic patients.
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We present a first systematic comparison of superluminous Type Ia supernovae (SNe Ia) at late epochs, including previously unpublished photometric and spectroscopic observations of SN 2007if, SN 2009dc and SNF20080723-012. Photometrically, the objects of our sample show a diverse late-time behaviour, some of them fading quite rapidly after a light-curve break at ∼ 150-200 d. The latter is likely the result of flux redistribution into the infrared, possibly caused by dust formation, rather than a true bolometric effect. Nebular spectra of superluminous SNe Ia are characterized by weak or absent [Fe III] emission, pointing at a low ejecta ionization state as a result of high densities. To constrain the ejecta and Ni masses of superluminous SNe Ia, we compare the observed bolometric light curve of SN 2009dc with synthetic model light curves, focusing on the radioactive tail after ∼60 d. Models with enough Ni to explain the light-curve peak by radioactive decay, and at the same time sufficient mass to keep the ejecta velocities low, fail to reproduce the observed light-curve tail of SN 2009dc because of too much γ -ray trapping.We instead propose a model with ∼1M of Ni and ∼2 M of ejecta, which may be interpreted as the explosion of a Chandrasekhar-mass white dwarf (WD) enshrouded by 0.6-0.7 M of C/O-rich material, as it could result from a merger of two massive C/O WDs. This model reproduces the late light curve of SN 2009dc well. A flux deficit at peak may be compensated by light from the interaction of the ejecta with the surrounding material.
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Whey protein has been indicated to curb diet-induced obesity, glucose intolerance and delay the onset of type 2 diabetes mellitus. Here the effects of intact crude whey, intact individual whey proteins and beta-lactoglobulin hydrolysates on an enteroendocrine (EE) cell model were examined. STC-1 pGIP/neo cells were incubated with several concentrations of yogurt whey (YW), cheese whey (CW), beta-lactoglobulin (BLG), alpha-lactalbumin (ALA) and bovine serum albumin (BSA). The findings demonstrate that BLG stimulates EE cell proliferation, and also GLP-1 secretion (an effect which is lost following hydrolysis with chymotrypsin or trypsin). ALA is a highly potent GLP-1 secretagogue which also increases the intracellular levels of GLP-1. Conversely, whey proteins and hydrolysates had little impact on GIP secretion. This appears to be the first investigation of the effects of the three major proteins of YW and CW on EE cells. The anti-diabetic potential of whey proteins should be further investigated.
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Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretin hormones released from intestinal enteroendocrine (EE) cells and have well-established glucose-lowering actions. Lactic acid bacteria (LAB) colonise the human intestine, but it is unknown whether LAB and EE cells interact. Acute co-culture of LAB with EE cells showed that certain LAB strains elicit GLP-1 and GIP secretion (13-194-fold) and upregulate their gene expression. LAB-induced incretin hormone secretion did not appear to involve nutrient mechanisms, nor was there any evidence of cytolysis. Instead PCR array studies implicated signalling agents of the toll-like receptor system, e.g. adaptor protein MyD88 was decreased 23-fold and cell surface antigen CD14 was increased 17-fold. Mechanistic studies found that blockade of MyD88 triggered significant GLP-1 secretion. Furthermore, blocking of CD14 completely attenuated LAB-induced secretion. A recent clinical trial clearly shows that LAB have potential for alleviating type 2 diabetes, and further characterisation of this bioactivity is warranted.
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Metabolic alterations have been identified as a frequent event in cancer. This is often associated with increased flux through glycolysis, and also a secondary pathway to glycolysis, hexosamine biosynthetic pathway (HBP). HBP provides substrate for N-linked glycosylation, which occurs in the endoplasmic reticulum and the Golgi apparatus. N-linked glycosylation supports protein folding and correct sorting of proteins to plasma membrane and secretion. This process generates complex glycoforms, which can be recognized by other proteins and glycosylation of receptor tyrosine kinases (RTK) can also regulate their plasma-membrane retention time. Of special interest for experimental biologists, plants produce proteins, termed lectins, which bind with high specificity to glyco-conjugates. For the purposes of molecular biology, plant lectins can be conjugated to different moieties, such as agarose beads, which enable precipitation of specifically glycosylated proteins. In this chapter, we describe in detail how to perform pull-down experiments with commercially available lectins to identify changes in the glycosylation of RTKs.
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Assessment of Human papillomavirus (HPV) prevalence and genotype distribution is important for monitoring the impact of prophylactic HPV vaccination. This study aimed to demonstrate the HPV genotypes predominating in pre-malignant and cervical cancers in Northern Ireland (NI) before the vaccination campaign has effect. Formalin fixed paraffin embedded tissue blocks from 2,303 women aged 16-93 years throughout NI were collated between April 2011 and February 2013. HPV DNA was amplified by PCR and HPV genotyping undertaken using the Roche® linear array detection kit. In total, 1,241 out of 1,830 eligible samples (68.0%) tested positive for HPV, with the majority of these [1,181/1,830 (64.5%)] having high-risk (HR) HPV infection; 37.4% were positive for HPV-16 (n=684) and 5.1% for HPV-18 (n=93). HPV type-specific prevalence was 48.1%, 65.9%, 81.3%, 92.2%, and 64.3% among cervical intraepithelial neoplasias (CIN) Grades I-III, squamous cell carcinomas (SCC) and adenocarcinoma (AC) cases, respectively. Most SCC cases (81.3%) had only one HPV genotype detected and almost a third (32.0%) of all cervical pathologies were HPV negative including 51.9% of CIN I (n=283), 34.1% CIN II (n=145), 18.7% of CIN III (n=146), 7.8% of SCC (n=5), and 35.7% of AC (n=5) cases. This study provides important baseline data for monitoring the effect of HPV vaccination in NI and for comparison with other UK regions. The coverage of other HR-HPV genotypes apart from 16 and 18, including HPV-45, 31, 39, and 52, and the potential for cross protection, should be considered when considering future polyvalent vaccines.
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Selective GLP-1 secretagogues represent a novel potential therapy for type 2 diabetes mellitus. This study examined the GLP-1 secretory activity of the ethnomedicinal plant, Fagonia cretica, which is postulated to possess anti-diabetic activity. After extraction and fractionation extracts and purified compounds were tested for GLP-1 and GIP secretory activity in STC-1 pGIP/neo cells. Intracellular levels of incretin hormones and their gene expression were also determined. Crude F. cretica extracts stimulated both GLP-1 and GIP secretion, increased cellular hormone content, and upregulated gene expression of proglucagon, GIP and prohormone convertase. However, ethyl acetate partitioning significantly enriched GLP-1 secretory activity and this fraction underwent bioactivity-guided fractionation. Three isolated compounds were potent and selective GLP-1 secretagogues: quinovic acid (QA) and two QA derivatives, QA-3β-O-β-D-glycopyranoside and QA-3β-O-β-D-glucopyranosyl-(28→1)-β-D-glucopyranosyl ester. All QA compounds activated the TGR5 receptor and increased intracellular incretin levels and gene expression. QA derivatives were more potent GLP-1 secretagogues than QA. This is the first time that QA and its naturally-occurring derivatives have been shown to activate TGR5 and stimulate GLP-1 secretion. These data provide a plausible mechanism for the ethnomedicinal use of F. cretica and may assist in the ongoing development of selective GLP-1 agonists.
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Effective collision strengths for electron-impact excitation of the phosphorus-like ion Cl III are presented for all fine-structure transitions among the levels arising from the lowest 23 LS states. The collisional cross sections are computed in the multichannel close-coupling R-matrix approximation, where sophisticated configuration-interaction wave functions are used to represent the target states. The 23 LS states are formed from the basis configurations 3s23p3, 3s3p4, 3s23p23d, and 3s23p24s, and correspond to 49 fine-structure levels, leading to a total possible 1176 fine-structure transitions. The effective collision strengths, obtained by averaging the electron collision strengths over a Maxwellian distribution of electron velocities, are tabulated in this paper for all 1176 transitions and for electron temperatures in the ranges T(K)=7500-25,000 and log T(K)=4.4-5.4. The former range encompasses the temperatures of particular importance for application to gaseous nebulae, while the latter range is more applicable to the study of solar and laboratory-type plasmas. © 2001 Academic Press.
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Die für die Abteilung Information und Kommunikation der Fakultät III, Medien, Information und Design – MID (im Folgenden: Abteilung IK) der Fachhochschule Hannover erarbeiteten „Empfehlungen für die Gestaltung schriftlicher Arbeiten“ bieten Anregungen und Erläuterungen zur formalen Gestaltung von schriftlichen Arbeiten, die von den Studierenden im Laufe ihres Studiums an der Abteilung IK als Studien- oder Prüfungsleistungen zu erbringen sind. Sie bringen teilweise ausführliche Beispiele und legen beson-deres Gewicht auf eine Darstellung der Zitiertechnik und der Zitierregeln (auch von Internet-Dokumenten). Weitere Schwerpunkte dieser Empfehlungen sind besondere Richtlinien für die Gestaltung von Diplom- oder Bachelorarbeiten, eine Auflistung der diesen Empfehlungen zugrunde gelegten Literatur und Anhänge (mit Beispielen zur Gestaltung von Titelseiten und Inhaltsverzeichnissen).
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Bei der vorliegenden Arbeit handelt es sich um eine überarbeitete Version einer Hausarbeit im Modul Research Management im Masterstudiengang Unternehmensentwicklung im Sommersemester 2014 bei Prof. Dr. Sven Litzcke. In der Arbeit wird untersucht, ob die oftmals vorherrschende Meinung zutrifft, dass Studierende wirtschaftsorientierter Studiengänge ihre Studiengangwahl aufgrund der positiven Karriere- und Verdienstmöglichkeiten und unter Vernachlässigung ihrer persönlichen Neigungen und Interessen getroffen haben. Mittels eines Fragebogens werden die Ausprägungen der Motivationsformen extrinsische und intrinsische Motivation von Studierenden der Fakultät IV Wirtschaft und Informatik der Hochschule Hannover gemessen. Da Studierenden von künstlerischen und kreativen Studiengängen dieses Verhalten nicht unterstellt wird, werden Studierende der Fakultät III Medien, Information und Design der Hochschule Hannover als Vergleichsgruppe herangezogen. Die Untersuchung orientiert sich an der Hypothese, dass die extrinsische Motivation von Studierenden der Fakultät IV der Hochschule Hannover in Bezug auf ihr Studium stärker ausgeprägt ist als die von Studierenden an der Fakultät III der Hochschule Hannover. Da vermutet wird, dass die Fakultät IV der Hochschule Hannover nicht aus einer homogenen Gruppe besteht, untersucht diese Arbeit zudem die Hypothese, dass die extrinsische Motivation von Studierenden im Studiengang Betriebswirtschaftslehre in Bezug auf ihr Studium stärker ausgeprägt ist, als die von Studierenden der Angewandten Informatik. Die Auswertung von 312 Fragebögen hat beide Hypothesen bestätigt. Studierende der Fakultät III sind weniger extrinsisch und stärker intrinsisch motiviert als Studierende der Fakultät IV. Zudem sind Studierende der Betriebswirtschaftslehre an der Hochschule Hannover stärker extrinsisch motiviert als Studierende der Angewandten Informatik an der Hochschule Hannover.
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In der vorliegenden Arbeit werden die Kosten für die Produktion von Speisequark mager und Speisequark 40 % F.i.Tr. für zwei Kapazitätsgrößen von 4.800 bzw. 9.500 kg Km/h nach einer speziellen Form der Teilkostenrechnung bestimmt. Bei Variationen der Kapazitätsauslastung (Pro duktionstage X Produktionsstunden/Tag) und der Produktanteile ergeben sich Kosten zwischen 11,99 und 18,95 Pf pro Becher Speisequark mager bzw. 11,73 und 18,45 Pf je Becher Speisequark 40% F.i.Tr. Das entspricht einer Differenz in den Stückkosten von durchschnittlich 27,5 Pf/kg Speisequark. Es zeigt sich dabei, daß die Kostendegression bedeutend stärker durch den Grad der Kapazitätsauslastung als durch die Kapazitätsgröße beeinflußt wird.
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Im Rahmen dieses Beitrages wird die Wechselwirkung zwischen abteilungsspezifischen Produktionskosten und der Struktur von Produktionsabteilungen für die Herstellung von Schnittkäse untersucht. Die Analyse eventueller Struktureffekte geschieht in zwei Schritten: zuerst wird der Einfluß unterschiedlicher Kapazitätsgrößen und -auslastungen von Käsereiabteilungen auf die Produktionskosten bestimmt. Danach wird der Frage nachgegangen, wie die Produktionsstrukturen für Schnittkäse in der BR Deutschland aussehen und welche Kosteneinsparungspotentiale sich bei moderaten Strukturveränderungen ergeben.